Screening
ion channel screening – has anything changed?
8 M Drug Discovery World Fall 2011
No review of ion channel screening over the past decade can avoid discussing the pivotal role played by automated electrophysiology. Arguably this technology, more than any other, has opened up the field to wider investigation, made ion channels more accessible as drug targets and facilitated the drive towards highest possible data quality. In this review we will hear how automated patch clamping systems are continuing to evolve and are increasingly positioned at the centre of most ion channel discovery activities.
any advances have been made in ion channel screening over the past decade. From a technology perspective perhaps the greatest of these was the emergence of the pla- nar patch used in automated patch clamping (APC) devices which has opened up the possibility of higher throughput direct electrophysiological assay of ion channel activity. However, the deployment of APC in screening was initially met with some skepticism by electrophysiology purists in the industry1. APC has evolved considerably in recent years with a diversity of new third generation sys- tems now addressing both voltage and ligand- gated channels at much higher throughputs and at higher seal resistances. In addition, the use of pop- ulation patch clamp and multi-hole approaches has largely mitigated initial concerns over data consis- tency and patch success rates. Many of the newer APC systems utilise cutting edge developments in
microfluidics. APC systems have also played a piv- otal role in enabling the early (non-compliant) investigation of hERG. Increasingly primary and stem cells are being used in ion channel testing and investigated by APC. Although screening technolo- gy has been regarded as the key to successful ion channel drug development2, the growing realisa- tion that leads discovered against ion channel tar- gets are less likely to make it through to the mar- ket than candidates from other disease areas has lead to the recent realignment or closure of some Pharma ion channel screening programmes and this is expected to promote greater reliance on biotech collaborations and outsourced testing. HTStec first got involved in tracking develop- ments of the ion channel screening market in 2004, and it is the only area where annual report updates have been undertaken, thanks largely to the interest and support of the vendor community.
By Dr John Comley
years of surveying
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